Outpatient Treatment with ¹³¹I-Anti-B1 Antibody: Radiation Exposure to Family Members

Patients

Twenty-two patients received intravenous radioimmunotherapy with ¹³¹I-anti-B1 monoclonal antibody. Patients were administered a therapeutic amount calculated to deliver a nonmyeloablative total-body absorbed dose (30–75 cGy) as part of several different clinical research protocols. The administered therapy dose was based on the patient’s total-body residence time, which was determined from an initial dosimetric study (14).

Patient-Specific Dose Calculation

According to the regulatory guidance, patients may be released on the basis of specific conditions. The following equations were used to calculate the total effective dose equivalent to individuals exposed to the patient for an infinite time (derivations of these equations are discussed in the Appendix):

On the basis of administered activity: Eq. 1 On the basis of the patient’s dose rate: Eq. 2 where D(∞) is the total effective dose equivalent (millisieverts) to the maximally exposed individual over an infinite time, Q₀ is the administered activity (megabecquerels), T_eff is the patient’s total-body effective half-time (days) determined by measurements after a tracer dose, T_eff is 0.693 × τ (residence time) under the condition of modeling whole-body retention as a single exponential, and D_r is the dose rate (mSv/h) at 1 m from the patient immediately after therapeutic administration.

The release criteria calculated using the administered activity (Eq. 1) are more conservative than those calculated using the patient’s dose rate (Eq. 2), because no attenuation of the radiation by the body is considered. With the release limit of D(∞) < 5 mSv (500 mrem), Equations 1 and 2 can be rearranged as follows to determine maximum administered activity or patient dose rate for patient release (i.e., either Eq. 3 or Eq. 4 must be true to allow release): Eq. 3 Eq. 4

These calculations take into account internal dose contribution and are based on conservative assumptions given in regulatory guide 8.39 (2). For example, regulatory guide 8.39 assumes that for the first 8 h after administration of radioiodine, 80% of the radioactivity is not voided from the urinary bladder (e.g., eliminated solely by the 8-d physical decay of ¹³¹I) and that the occupancy factor (the fraction of time that the maximally exposed individual is within 1 m of the patient) is 0.75 for this initial period.

If the actual administered activity is less than the activity determined according to Equation 3, then the patient is releasable according to the new NRC regulations. Equation 3 involves the use of only a single patient-specific factor (i.e., effective half-time), which must be included in the patient’s record at the time of release. Equation 4 was also used to determine the releasibility of the patient. In this case, a second patient-specific factor, the patient’s dose rate at 1 m, which accounts for attenuation, must also be included in the patient’s record at the time of release. The dose rate is measured after the therapeutic administration. All the calculations assume the use of an occupancy factor of 0.25 after the initial 8-h nonvoiding period. The occupancy factor is the fraction of time that an individual is assumed to be 1 m away from the released patient. If there is justification for using a lower occupancy factor of 0.125, or if a higher occupancy factor of 0.5 or more is indicated, then the calculated values must be changed accordingly (5,7).

For the ¹³¹I-anti-B1 antibody protocol, data indicate that a more appropriate assumption is that an initial nonvoiding period of 3 h can be used, instead of the 8-h period suggested by the NRC. A 3-h period is more appropriate because it has been shown to be a conservative estimate for the time of the first voiding of the urinary bladder (15) and because it is consistent with the analysis performed on 109 ¹³¹I-anti-B1 antibody patient studies (6). The conservative nature of this 3-h assumption is further supported by the fact that ¹³¹I-anti-B1 antibody is absorbed instantaneously because of its intravenous administration, whereas regulatory guide 8.39 assumed oral administration. Additionally, for this initial nonvoiding period, it makes sense to account for 100% of the administered activity and not the 80% recommended in regulatory guide 8.39.Using these assumptions and the fact that R/h = Γ Q₀/r², the dose over an infinite time to the exposed individual becomes: Eq. 5

This equation was also used to project the dose for infinite time in this study.

Guidelines

If the calculations indicate that the patient is releasable, one then determines whether the patient can actually be released. Patients containing >1.22 GBq (33 mCi) ¹³¹I (or with a dose rate > 0.07 mSv/h [7 mrem/h] at 1 m) can be released if one can show that no individual who comes into contact with the patient is likely to receive a dose > 5 mSv. The release is dependent on the circumstances of each patient. Interviewing the patient and using that information to determine whether the patient may be released are essential. Factors to consider include the patient’s ability to understand and willingness to follow written instructions, the patient’s ability to care for himself or herself, the patient’s ability to refrain from returning to work if necessary, the patient’s exposure to others while returning home after treatment, and the presence of urinary incontinence. The form that we used to interview patients is shown in Figure 1. Once the patient interview is completed, the responsible physician or radiation safety officer evaluates whether the patient can be released. If the determination is affirmative, discharge instructions are given to the patient.

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FIGURE 1.

Form used to determine whether patient can be released from hospital after radioimmunotherapy with ¹³¹I-anti-B1 antibody. S/N = serial number.

Instructions to Patients and Caregivers

Once the release has been determined, the patient must be provided with written instructions to comply with the provisions of 10 CFR 35.75(b). The instructions and all related discussions must be in a simple and clear format so that the patient can understand their importance. Specific instructions were developed to address the unique requirements of patients treated with the ¹³¹I-anti-B1 antibody to maintain exposures ALARA to other individuals.

Patient discharge instructions for various activities (e.g., using public transportation, attending to personal hygiene, and maintaining distance from others) were developed using exposure data obtained from patients who had been treated with ¹³¹I-anti-B1 antibody and confined under the old release regulations and by making assumptions about the distances at which individuals typically interact with each other in various social situations. A diary was kept by the maximally exposed individual to record the times that the radiation monitoring device was worn and the interactions with the patient.

The radiation safety discharge instructions were provided to and discussed with the patients and caregivers (if possible) by the nuclear medicine physician or radiation safety personnel before the release of the patient. Any questions about radiation safety issues were answered at that time. One copy of these written instructions was provided to the patient, and a second copy was maintained in the patient’s files.

Radiation Monitoring

Family members received film badges, thermoluminescent dosimeters (TLDs), OSLs, or electronic digital dosimeters. In most cases, the caregiver was given more than a single type of device. Radiation safety personnel taught the caregivers how to wear and use the devices. The caregivers were also asked to log their activities and resultant exposures to verify the appropriateness of the discharge instructions and to confirm that the radiation doses to the family members were below the regulatory limits. The readings were also compared with the theoretic doses over an infinite time predicted by the patient-specific calculations.

Data Analysis

All radiation monitoring devices were processed on return. Diaries of the direct-reading dosimeters were reviewed, and the readings were transferred to spreadsheets for subsequent analyses. The final dosimeter reading was used to calculate the predicted dose over an infinite time based to the maximally exposed individual using the following equation: Eq. 6 where D(∞) is the total effective dose equivalent (millisieverts) to the maximally exposed individual and N is the number of days the individual was monitored. This “measured” dose for infinite time was compared with the doses for infinite time predicted by Equations 1, 2, and 5.

NRC Default Tables and Patient-Specific Calculations

Regulatory guide 8.39 (2) provides default tables with values authorizing patient release based on administered activities or 1-m patient dose rates for a variety of radionuclides. The values calculated for both tables are based solely on the physical half-life of the radionuclide (i.e., no biologic elimination is assumed). The equation used to calculate these release values is essentially the same as introduced in 1970 by National Council on Radiation Protection and Measurements report no. 37 (16) with the exception of the occupancy factor. The selection of an occupancy factor of 0.25 at 1 m for estimating the ¹³¹I dose to an individual from exposure to a released patient is based on the professional judgment of time–distance combinations that are likely after instructions to minimize time near the patient.

Use of the physical half-life, not the effective half-life, of the radionuclide assumes that the body retains the radionuclide (e.g., ¹³¹I) until it is fully decayed and that none is cleared through biologic processes. Clearly, this is not true: biologic processes do affect the clearance of radionuclides. Patients receiving ¹³¹I therapy do not retain radioactivity for the physical half-life of the radionuclide. Rather, patients eliminate ¹³¹I more quickly because of biologic elimination. As a result, the patient-specific dose calculations, which take into account both the physical and the biologic half-life (i.e., the effective half-life) of the radionuclide, are more complete and appropriate than the NRC default tables in calculating the dose an individual will likely receive if exposed to a patient treated with ¹³¹I (7). Because the default tables do not take into account the biologic elimination of the radionuclide, their use will overestimate the dose an individual would receive if exposed to a patient treated with ¹³¹I. Using a patient-specific dose calculation provides a more complete and appropriate estimation of dose.

Direct measurements are the best way to obtain the dose any individual is likely to receive under realistic exposure conditions. Three previous studies (17–19) measured doses to family members from patients who were released after treatment of thyroid cancer or hyperthyroidism with <1.11 GBq (30 mCi) ¹³¹I. These studies showed that use of only the physical half-life in calculations will overestimate radiation doses received by family members and suggested that the patient-specific dose calculation will be conservative. These data are summarized in Table 1A. On the basis of these 3 studies, a regulatory analysis (3) concluded that the revised NRC patient-release rule provides an adequate level of protection, with a significant margin of safety for patients who make a reasonable effort to follow instructions. Therefore, both professional judgment and empiric measurements support the validity of using the patient-specific dose calculation in determining the maximum likely radiation dose to another individual. The radiation dose predicted by the calculation is usually significantly higher than the dose obtained by direct measurements with film badges or TLDs worn by the family members of the patients.

Regulatory guide 8.39 allows the licensee to release patients on the basis of patient-specific calculations, including using the biologic or effective half-life. The procedure for calculating doses based on patient-specific factors is given in Appendix B of the regulatory guide. To account for the time for ¹³¹I to be absorbed from the stomach and the holdup of iodine in the urine while in the bladder, the regulatory guide conservatively makes the following assumptions: during the first 8 h after administration, 80% of the ¹³¹I is removed from the body by only the physical decay of ¹³¹I, and the occupancy factor for this 8-h nonvoiding period is assumed to be 0.75 (0.25 after this period).

The University of Nebraska Medical Center has performed several ¹³¹I-anti-B1 antibody therapies since late 1996. In all cases, a monoexponential clearance rate has been observed. Using the assumptions of the regulatory guide for the initial 8-h period and a monoexponential clearance after this nonvoiding period, and taking into account the internal dose contribution from ¹³¹I (Eq. B-6 in the regulatory guide), the following equation based on a point source geometry determines the dose for infinite time to the maximally exposed individual: Eq. 1A where D(∞) is the dose for an infinite time to the maximally exposed individual (millisieverts); Q₀ is the administered activity (megabecquerels); 34.6 is a conversion factor of 24 h/d divided by ln2 (resulting from integration); Γ is the γ-ray constant, which is 0.595 mSv-cm²/MBq-h for ¹³¹I; E₁ is the occupancy factor for the first 8 h, or 0.75; E₂ is the occupancy factor after 8 h, or 0.25; T_p is 8.04 d; T_eff is the effective half-life (days) based on the patient’s dosimetric dose (e.g., the initial 185-MBq [5 mCi] dose administered to calculate the activity required for that patient’s therapy); and 0.000143 is a factor derived from regulatory guide 8.39.When multiplied by Q₀, this factor gives the internal dose contribution in millisieverts. On simplification, the equation for dose for infinite time becomes: Eq. 2A

Using the patient dose rate at 1 m (D_r), the equation for dose for infinite time becomes: Eq. 3A where D_r is the patient dose rate at 1 m (mSv/h). The administered activity and dose rate at which the patient may be released can be determined by setting the dose for infinite time in Equations 2A and 3A to 5 mSv (500 mrem) and solving for the corresponding parameter as follows: Eq. 4A Eq. 5A